P556: CHANGES IN HEALTH-RELATED QUALITY OF LIFE IN PATIENTS WITH NEWLY-DIAGNOSED ACUTE MYELOID LEUKEMIA RECEIVING IVOSIDENIB + AZACITIDINE OR PLACEBO + AZACITIDINE
Authors: A. Schuh, S. de Botton, C. Recher, S. Vives Polo, E. Zarzycka, J. Wang, G. Bertani, M. Heuser, R. Calado, S.-P. Yeh, J. Hui, S. Pandya, D. Gianolio, C. Chamberlain, H. Dohner, P. Montesinos
Journal: HemaSphere (2022)

Background: Ivosidenib (IVO) is a potent, targeted inhibitor of mutant isocitrate dehydrogenase 1 (mIDH1) that is approved for acute myeloid leukemia (AML). IVO plus azacitidine (AZA) demonstrated clinical benefit compared with placebo and AZA in the AGILE study (NCT03173248). Aims: To assess the impact of IVO+AZA versus placebo+AZA on health-related quality of life (HRQoL) using data from the AGILE study. Methods: In the double-blind, placebo-controlled phase 3 AGILE study, patients (pts) were randomized 1:1 to IVO 500 mg QD + AZA 75 mg/m2 SC or IV for 7 days in 28-day cycles, or placebo+AZA. HRQoL was a secondary endpoint assessed using two validated questionnaires: the European Organisation of Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30) and the EuroQol 5-dimension 5-level questionnaire (EQ-5D-5L). Questionnaires were administered pre-dose on cycle (C) 1 Day (D) 1, on C1D15, C2D1, C2D15, and on D1 of every odd cycle thereafter until the end of treatment. Score change from baseline across visits for all subscales of EORTC QLQ-C30 was analyzed with mixed models. A 10-point threshold in EORTC QLQ-C30 subscale score was used to evaluate clinically meaningful changes from baseline or differences between arms. Two-sided nominal p-values are reported. All patients gave written informed consent. Results: At baseline, 69 and 68 pts out of 72 receiving IVO+AZA completed the EORTC QLQ-C30 and EQ-5D-5L, respectively, and 66 pts out of 74 receiving placebo+AZA completed both. Mean baseline HRQoL scores were similar between treatment arms (EORTC QLQ-C30 global health status [GHS/QoL] score was 56.3 and 53.2 in the IVO+AZA and placebo+AZA arms, respectively). There was an initial decline in HRQoL (EORTC QLQ-C30 GHS/QoL) in both arms for ~4 months, consistent with time to response, and which was generally not clinically meaningful (Table). IVO+AZA was associated with preserved or improved HRQoL compared to baseline for most subscales of the EORTC QLQ-C30 from C5 to C19 (after which no placebo+AZA HRQoL data were available), and at most timepoints for EQ-5D-5L VAS scores and index values. EORTC QLQ-C30 subscales with clinically meaningful improvements from baseline at most timepoints from C5 to C19 in the IVO+AZA arm included GHS/QoL (Table), fatigue, pain and appetite loss. In contrast, there were few clinically meaningful improvements from baseline in placebo+AZA pts. GHS/QoL scores were significantly improved (p≤0.05) for IVO+AZA versus placebo+AZA at C2D1, C2D15, C7 and C9 (Table), and differences between treatment arms were clinically meaningful at C2D1, C2D15, C7, C9, C13, C15 and C19 (Table). Likewise, improvements in EORTC QLQ-C30 fatigue, appetite loss, nausea and vomiting, diarrhea, cognitive functioning and social functioning favored IVO+AZA over placebo+AZA at multiple timepoints. Image:Summary/Conclusion: Data from the AGILE study show that patients with mIDH1 AML receiving treatment with IVO+AZA tended to report maintenance or improved HRQoL from cycle 5 through to cycle 19 compared with placebo+AZA.